Lorcaserin

Identification

Name

Lorcaserin

Accession Number

DB04871

Type

Small Molecule

Groups

Approved

Description

Lorcaserin (previously APD-356), a highly selective 5HT2C receptor agonist, is used for the treatment of obesity. It has been shown to reduce body weight and food intake in animal models of obesity, and it is thought that targeting the 5HT2C receptor may alter body weight by regulating satiety. Lorcaserin is marketed as a salt form called Belviq, which is lorcaserin hydrochloride.

Pharmacology

Lorcaserin produced a dose-dependent weight loss over a 12-week period by promoting satiety and decreasing food consumption.

Mechanism of action

Although the exact mechanism is unknown, it is believed to involve the selective activation of 5-HT2C receptors in the anorexigenic pro-opiomelanocortin neurons in the arcuate nucleus of the hypothalamus. This results in decreased food intake and satiety by promoting the release of alpha-melanocortin stimulating hormone, which acts on melanocortin-4 receptors.

Lorcaserin has a peak plasma concentration of about 1.5 - 2 hours, but the bioavailability was not determined.

Volume of distribution

The volume of distribution was not determined, but lorcaserin distributes to the central nervous system and cerebrospinal fluid.

Protein binding

Lorcaserin hydrochloride has a plasma protein binding of approximately 70%.

Metabolism

Lorcaserin has extensive hepatic metabolism producing inactive compounds. Lorcaserin sulfamate (M1) is the major metabolite circulating in the plasma, and N-carbamoyl glucuronide lorcaserin (M5) is the major metabolite in urine. Other minor metabolites that are both excreted in urine are glucuronide or sulfate conjugates.

Lorcaserin is eliminated by hepatic metabolism, and the metabolites are eliminated mostly in the urine (92.3%) and some through feces (2.2%).

Half life

The plasma half life is approximately 11 hours.

Clearance

The clearance value was not determined.

Toxicity

Most common adverse reactions include hypoglycemia (diabetic patients), headache,
back pain,fatigue, decrease in lymphocytes,upper respiratory tract infection, and nasopharyngitis. Moreover, the safety and efficacy of coadministration with other weight loss products has not been established, and cardiovascular effects on mortality and morbidity have not been established.

Taxonomy

Description

This compound belongs to the class of organic compounds known as benzazepines. These are organic compounds containing a benzene ring fused to an azepine ring (unsaturated seven-membered heterocycle with one nitrogen atom replacing a carbon atom).